scholarly journals The Effects of Aging on Indices of Oxidative Stress and Apoptosis in the Female Fischer 344/Nnia X Brown Norway/BiNia Rat Heart

2013 ◽  
Vol 7 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Jacqueline Fannin ◽  
Kevin M. Rice ◽  
Srininvas Thulluri ◽  
Ravi Kumar Arvapalli ◽  
Paulette Wehner ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Caspase 3 ◽  
Nitrosative Stress ◽  
Descriptive Study ◽  
Female Rats ◽  
Brown Norway ◽  
Rodent Models ◽  
Fischer 344 ◽  
Stress Markers ◽  
Effects Of Aging

Oxidative-nitrosative stress may play a role in age-associated cardiovascular disease as implied by recent studies.However, limited research has been conducted using aged female rodent models. In this study, we examined hearts obtained from 6-, 26-, and 30-month old female Fischer 344/Nnia x Brown Norway/BiNia (F344xBN) rats in order to examine how aging affects levels of cardiac oxidative-nitrosative stress and apoptosis. Oxidative (superoxide anion and 4-HNE) and nitrosative (protein nitrosylation) stress markers were increased 180 ± 17 %, 110 ± 3 %, and 14 ± 2 %, respectively in 30-month hearts compared to the hearts of 6-month female rats. Coincident with these changes in oxidative-nitrosative stress, aging was also found to be associated with increases in the number of Tdt-mediated dUTP nick labeling (TUNEL)-positive cardiomyocytes, alterations in the Bax/Bcl-2 ratio, and elevated cleavage of caspase-3. Regression analysis demonstrates significant correlation in the age-associated changes markers of oxidative–nitrosative stress with changes in apoptotic signaling. The findings from this descriptive study imply that age-associated increases in mitochondrial-mediated apoptosis may be associated with the increase in oxidative-nitrosative stress in the aging F344xBN female heart.

scholarly journals Effects of Aging and Renin‐Angiotensin System (RAS) Blockade on the Intra‐renal RAS in Older Fischer 344 X Brown Norway Rats

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Sherry O Kasper ◽  
Shea Gilliam‐Davis ◽  
Leanne Groban ◽  
Christy S Carter ◽  
William E Sonntag ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Brown Norway ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fischer 344 ◽  
Effects Of Aging ◽  
Norway Rats

Abstract P185: Role of Ucp2 in the Oxidative/nitrosative Stress-mediated Hypertension Associated with Dj-1 Depletion

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Carmen De Miguel ◽  
William C Hamrick ◽  
Laureano Asico ◽  
Pedro Jose ◽  
Santiago Cuevas
Keyword(s):  
Er Stress ◽  
Caspase 3 ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Stress Markers ◽  
Markers Of Inflammation ◽  
Caspase 12 ◽  
Ucp2 Expression ◽  
Renal Proximal Tubule Cells ◽  
Species Production

DJ-1 -/- mice, relative to wild-type (WT) littermates, have increased blood pressure (BP) ( DJ-1 -/- :130±4 vs WT:100±3 mmHg, n=6/8). and renal expressions of nitro-tyrosine (+76±31% of WT mice, n=5) and malondialdenyde (+63±23% of WT mice, n=4). Tempol, a superoxide dismutase mimetic, decreased the BP of DJ-1 -/- mice ( DJ-1 -/- : before tempol:119±3; after tempol:100±1 mmHg vs WT, n=4) and renal malondialdehyde production ( DJ-1 -/- : before tempol:+40±5%; after tempol:-24±5% vs WT, n=4) but increased serum nitrate/nitrite levels (+72±30%, n=4), indicating the presence of both oxidative and nitrosative stress. Lack of DJ-1 makes some cells vulnerable to endoplasmic reticulum (ER) stress. However, renal mRNA expression of ER stress markers, GRP94, ATF-4, ATF-6, sXBP-1, CHOP, caspase-12, and caspase-3 was not different between DJ-1 -/- and WT (n=7) mice. Markers of inflammation, IL-6, TNF α, MCP-1, NFκB, and T-cell and macrophage infiltration, were also not increased in the kidney of DJ-1 -/- mice. By contrast, renal mitochondrial (mt) HSP60, but not mtHSP40, was increased in DJ-1 -/- mice (2.9±0.1 fold, n=4) but there were no changes in the renal mRNA expressions of Nix/BNIP3L, BNIP3, PINK, FIS1, MFN1, MFN2, PPRC1, NRF-1, and PGC1, indicating that mt oxidative stress did not affect mt function. The renal expression of UCP2, which is involved in the control of mt-reactive oxygen species production, was elevated in DJ-1 -/- mice (4.1±1.1 fold of WT, n=4). Silencing UCP2 in mouse renal proximal tubule cells (-0.46.5±0.01 fold) increased the expression of ER stress and apoptosis markers CHOP (2±0.4 fold), ATF4 (2.6±0.6 fold), caspase-3 (2.3±0.4 fold), and caspase-12 (1.7±0.2 fold)(n=3). There were no differences in renal renin expression, sodium excretion, and serum creatinine between DJ-1 -/- and WT mice (n=5). There were no abnormalities in renal morphology, including fibrosis, in the kidneys of DJ-1 -/- mice. However, urinary KIM-1 was increased in DJ-1 -/- mice (148±22% of WT mice, n=4) and decreased by tempol (-58±3%, n=4); renal UCP2 expression was also partially normalized by tempol (1.8±0.2 fold of WT, n=4). UCP2 may protect from the development of renal ER stress and damage in the mt oxidative/nitrosative stress associated with DJ-1 depletion.

Effects of aging on capillary geometry and hemodynamics in rat spinotrapezius muscle

2003 ◽  
Vol 285 (1) ◽  
pp. H251-H258 ◽  
Author(s):  
John A. Russell ◽  
Casey A. Kindig ◽  
Brad J. Behnke ◽  
David C. Poole ◽  
Timothy I. Musch
Keyword(s):  
Fiber Type ◽  
Structure And Function ◽  
Brown Norway ◽  
Diffusive Transport ◽  
Capillary Length ◽  
Performance Deficits ◽  
Fischer 344 ◽  
Muscle Aging ◽  
Effects Of Aging ◽  
And Function

The effects of aging on muscle microvascular structure and function may play a key role in performance deficits and impairment of O2 exchange within skeletal muscle of senescent individuals. To determine the effects of aging on capillary geometry, red blood cell (RBC) hemodynamics, and hematocrit in a muscle of mixed fiber type, spinotrapezius muscles from Fischer 344 × Brown Norway hybrid rats aged 6–8 mo [young (Y); body mass 421 ± 10 g, n = 6] and 26–28 mo [old (O); 561 ± 12 g, n = 6] were observed by high-resolution transmission light microscopy under resting conditions. The percentage of RBC-perfused capillaries (Y: 78 ± 3%; O: 75 ± 2%) and degree of tortuosity and branching (Y: 13 ± 2%; O: 13 ± 2%, additional capillary length) were not different in O vs. Y muscles. Lineal density of RBC-perfused capillaries in O was significantly reduced (Y: 30.7 ± 1.8, O: 22.8 ± 3.1 capillaries/mm; P < 0.05). However, RBC-perfused capillaries from O rats ( n = 78) exhibited increased RBC velocity ( VRBC) (Y: 219 ± 12, O: 310 ± 14 μm/s; P < 0.05) and RBC flux ( FRBC) (Y: 27 ± 2, O: 41 ± 2 RBC/s; P < 0.05) vs. Y rats ( n = 66). Thus O2 delivery per unit of muscle was not different between groups (Y: 894 ± 111, O: 887 ± 118 RBC · s-1 · mm muscle-1). Capillary hematocrit was not different in Y vs. O rats (Y: 26 ± 1%, O: 28 ± 1%: P > 0.05). These data indicate that in resting spinotrapezius muscle, aging decreases the lineal density of RBC-perfused capillaries while increasing mean VRBC and FRBC within those capillaries. Whereas muscle conductive O2 delivery and capillary hematocrit were unchanged, elevated VRBC reduces capillary RBC transit time and may impair the diffusive transport of O2 from blood to myocyte particularly under exercise conditions.

Effects of aging on single cardiac myocyte function in Fischer 344 x Brown Norway rats

2000 ◽  
Vol 279 (2) ◽  
pp. H559-H565 ◽  
Author(s):  
Philip A. Wahr ◽  
Daniel E. Michele ◽  
Joseph M. Metzger
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Cardiac Myocyte ◽  
Brown Norway ◽  
Rat Strains ◽  
Compensatory Mechanisms ◽  
Fischer 344 ◽  
Age Related ◽  
Effects Of Aging

The Fischer 344 x Brown Norway (F344xBN) rat has been demonstrated to have a lower incidence of age-related pathology than other rat strains. Therefore, to elucidate the effects of aging on cardiac function, uncomplicated by compensatory effects caused by age-related pathology, cardiac myocytes were isolated from female F344xBN rats at 6 (young) and 32–33 (old) mo of age. Myocytes showed an increase in the relative amount of β-myosin heavy chain with advanced age and a significant rightward shift in the tension-pCa curve from 5.78 ± 0.02 pCa units in young adult myocytes to 5.66 ± 0.03 pCa units. Consistent with a shift to a slower myosin isoform, the time from stimulation to peak sarcomere shortening increased with age from 50.5 ± 1.3 to 58.9 ± 1.0 ms. In contrast, no age-related difference was found in either the relengthening parameters or the Ca2+ transient, indicating that relaxation is not directly altered by aging. This latter finding is at variance with previous studies in rat strains with higher rates of pathology. We conclude, therefore, that the primary effect of aging in isolated cardiac myocytes from the F344xBN rat model is a shift in the myosin heavy chain isoform. Changes in relaxation seen in other rat strains may result from compensatory mechanisms induced by pathological conditions.

Aging increases venous compliance in awake instrumented rats

1993 ◽  
Vol 264 (6) ◽  
pp. H1948-H1952 ◽  
Author(s):  
M. R. Glick ◽  
J. D. Gehman ◽  
J. A. Gascho
Keyword(s):  
Volume Expansion ◽  
Filling Pressure ◽  
Brown Norway ◽  
Volume Depletion ◽  
Venous Compliance ◽  
Fischer 344 ◽  
Baseline Weight ◽  
Volume Relation ◽  
Effects Of Aging ◽  
Blood Volumes

To determine the effects of aging on total venous compliance, mean circulatory filling pressure (MCFP) was determined at several different blood volumes in 10 young (10-mo-old) and 10 older (30-mo-old) awake instrumented male Fischer 344/Brown Norway hybrid rats. Baseline weight and mean arterial pressure were similar in the two groups; heart rate was higher in the young (426 +/- 9 beats/min) than in the older rats (376 +/- 8 beats/min). Although MCFP was similar in the two groups at baseline blood volume, MCFP rose less with transient volume expansion and fell less with transient volume depletion in the older rats. The calculated venous compliance (reciprocal of the slope of the MCFP-to-volume relation) for the older rats was 25% greater than in the younger rats (3.28 +/- 0.21 vs. 2.63 +/- 0.12 ml.kg-1.mmHg-1; P = 0.014). In this conscious instrumented rat model, baseline total venous compliance is increased in older rats.

Altered regional blood flow responses to submaximal exercise in older rats

2004 ◽  
Vol 96 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Timothy I. Musch ◽  
Kevin E. Eklund ◽  
K. Sue Hageman ◽  
David C. Poole
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Submaximal Exercise ◽  
Brown Norway ◽  
Maximal Aerobic Capacity ◽  
Fischer 344 ◽  
Hindlimb Muscles ◽  
Effects Of Aging ◽  
Small And Large Intestine

Maximal aerobic capacity and the ability to sustain submaximal exercise (Ex) declines with advancing age. Whether altered muscle blood flow (BF) plays a mechanistic role in these effects remains to be resolved. The present investigation determined the effects of aging on the hemodynamic and regional BF response to submaximal Ex in rats. Heart rate (HR), mean arterial pressure (MAP), and BF to different organs (kidneys, splanchnic organs, and 28 hindlimb muscles) were determined at rest and during submaximal treadmill Ex (20 m/min, 5% grade) with radiolabeled microspheres in young (Y; 6-8 mo old, 339 ± 8 g, n = 9) and old (O; 27-29 mo old, 504 ± 18 g, n = 7) Fischer 344 × Brown Norway rats. Results demonstrated that HR, MAP, and BF to the pancreas, small and large intestine, and total hindlimb musculature were similar between Y and O rats at rest. BF to the kidneys, spleen, and stomach were 33, 60, and 43% lower, respectively, in O compared with Y rats. BF to the total hindlimb musculature increased ( P < 0.05) during Ex and was similar for both Y and O rats (Y: 16 ± 3 to 124 ± 7 vs. O: 20 ± 3 to 137 ± 12 ml·min-1·100 g-1). However, in O vs. Y rats, BF was reduced in 6 (highly oxidative) and elevated in 8 (highly glycolytic) of the 28 individual hindquarter muscles or muscle parts examined ( P < 0.05). During Ex, BF to the spleen and stomach decreased ( P < 0.05) from rest in Y rats, whereas BF decreased in the kidneys, pancreas, spleen, stomach, as well as the small and large intestines of O rats. In conclusion, these data demonstrate that, despite similar increases in total hindlimb BF in Y and O rats during submaximal Ex, there is a profound BF redistribution from highly oxidative to highly glycolytic muscles.

Effects of aging on executive functioning and mesocorticolimbic dopamine markers in male Fischer 344 × brown Norway rats

2018 ◽  
Vol 72 ◽  
pp. 134-146 ◽  
Author(s):  
Ryan J. Tomm ◽  
Maric T. Tse ◽  
Daniel J. Tobiansky ◽  
Helen R. Schweitzer ◽  
Kiran K. Soma ◽  
...  
Keyword(s):  
Executive Functioning ◽  
Brown Norway ◽  
Fischer 344 ◽  
Effects Of Aging ◽  
Norway Rats

Effects of aging on axon terminals in the dentate molecular layer

1987 ◽  
Vol 45 ◽  
pp. 928-929
Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova
Keyword(s):  
Granule Cells ◽  
Molecular Layer ◽  
Age Groups ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Perforant Path ◽  
Axon Terminals ◽  
Fischer 344 ◽  
Spatial Memory Deficit ◽  
Effects Of Aging

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.

scholarly journals Protective effect of Toxocara vitulorum extract against alpha-naphthylisothiocyanate-induced cholangitis in rat

2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Abeer Mahmoud Badr ◽  
Mohamed Farid ◽  
Ahmed Abdel Aziz Biomy ◽  
Ayman Saber Mohamed ◽  
Noha Ahmed Mahana ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Wistar Rat ◽  
Liver Function Tests ◽  
T Helper ◽  
Standard Drug ◽  
Toxocara Vitulorum ◽  
Stress Markers ◽  
Tnf Α ◽  
Ifn Γ ◽  
Antioxidant Markers

Abstract Background Cholestasis is the major cause of bile acid accumulation leading to liver damage. Chronic infection of worms can modulate the immune response towards T helper (Th)2-related cytokines. The present study aims to evaluate the protective impact of an ascarid nematode Toxocara vitulorum extract (TvE) against alpha-naphthylisothiocyanate (ANIT)-induced cholangitis male wistar rat model compared to ursodeoxycholic acid (UDCA) as a standard drug. Results Pretreatment with TvE and/or UDCA induced a marked reduction in the levels of liver function tests and malondialdehyde, while antioxidant markers were increased compared to cholestatic rats. Pretreatment with either TvE or combination before cholangitis induction attenuated the predominant Th1-related cytokines (IFN-γ and TNF-α) to Th2 (IL-13 and IL-10). TvE administration promoted higher expression levels of Bcl-2 protein and lower levels of caspase-3 compared to cholestatic rats. Conclusions Treatment with TvE has improved the liver functions and elevated the levels of oxidative stress markers. The upregulation of Th2-related cytokines and suppression of apoptosis through caspase-3 might be considered as a potential mechanism of TvE. Thereby, this natural extract revealed an opportunity for use in treatment of cholangitis disease.

scholarly journals Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 886
Author(s):  
Samar S. Elblehi ◽  
Yasser S. El-Sayed ◽  
Mohamed Mohamed Soliman ◽  
Mustafa Shukry
Keyword(s):  
Creatine Kinase ◽  
Caspase 3 ◽  
Date Palm ◽  
Nitrosative Stress ◽  
Troponin I ◽  
Troponin T ◽  
Heart Weight ◽  
Albino Rats ◽  
Pollen Extract ◽  
Date Palm Pollen

Doxorubicin (DOX) has a potent antineoplastic efficacy and is considered a cornerstone of chemotherapy. However, it causes several dose-dependent cardiotoxic results, which has substantially restricted its clinical application. This study was intended to explore the potential ameliorative effect of date palm pollen ethanolic extract (DPPE) against DOX-induced cardiotoxicity and the mechanisms underlying it. Forty male Wistar albino rats were equally allocated into Control (CTR), DPPE (500 mg/kg bw for 4 weeks), DOX (2.5 mg/kg bw, intraperitoneally six times over 2 weeks), and DPPE + DOX-treated groups. Pre-coadministration of DPPE with DOX partially ameliorated DOX-induced cardiotoxicity as DPPE improved DOX-induced body and heart weight changes and mitigated the elevated cardiac injury markers activities of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatine kinase-cardiac type isoenzyme. Additionally, the concentration of serum cardiac troponin I (cTnI), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and cytosolic calcium (Ca+2) were amplified. DPPE also alleviated nitrosative status (nitric oxide) in DOX-treated animals, lipid peroxidation and antioxidant molecules as glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities and inflammatory markers levels; NF-κB p65, TNF-α, IL-1β, and IL-6. As well, it ameliorated the severity of histopathological lesions, histomorphometric alteration and improved the immune-staining of the pro-fibrotic (TGF-β1), pro-apoptotic (caspase-3 and Bax), and anti-apoptotic (Bcl-2) proteins in cardiac tissues. Collectively, pre-coadministration of DPPE partially mitigated DOX-induced cardiac injuries via its antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic potential.

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